Total Synthesis of the Biphenyl Alkaloid (−)‐Lythranidine

A sequence comprising a ring‐closing alkyne metathesis of a propargyl alcohol derivative, followed by a ruthenium‐catalyzed redox isomerization of the derived cycloalkyne and a transannular aza‐Michael addition allowed the formation of the distinguishing piperidine‐metacyclophane framework of the Lythraceum alkaloid lythanidine in a few high‐yielding steps. This application attests to the excellent functional‐group tolerance of a molybdenum alkylidyne complex endowed with triphenylsilanolate ligands, which enabled the macrocyclization even in the presence of protic functionalities, and thus illustrates the power of contemporary catalytic acetylene chemistry for target‐oriented synthesis.     

Cross‐Metathesis/Isomerization/Allylboration Sequence for a Diastereoselective Synthesis of Anti‐Homoallylic Alcohols from Allylbenzene Derivatives and Aldehydes

We describe a highly diastereoselective approach to anti‐homoallylic alcohols from allylbenzene derivatives and aldehydes. The strategy is based on a cross‐metathesis/isomerization/allylboration sequence catalyzed successively by ruthenium and iridium. This methodology provides another way to access this class of compounds, which leads to the preparation of hitherto‐unknown homoallylic alcohols without the requirement to control the stereochemistry of the 1‐alkenyl boronate intermediates. Our study towards an enantioselective version of this sequential reaction is also reported.     

Synthesis of N‐Tosylhomosphinganine and N‐Tosylsedridine

A straightforward synthesis of N‐tosylhomosphinganine and N‐tosylsedridine has been achieved from trans‐4‐hydroxyproline by Grignard addition, regioselective Baeyer‐Villiger reaction, cross or ring‐closing metathesis and hydrogenation as the key steps.     

Light‐Mediated Total Synthesis of 17‐Deoxyprovidencin

An asymmetric synthesis of the diterpenoid 17‐deoxyprovidencin is described. Key steps include an aldol addition, a base‐catalyzed Wipf‐type furan formation, a Z‐selective ring‐closing metathesis for macrocyclization, a photochemical E/Z isomerization to a highly strained and conformationally restricted ring system, and the stereoselective formation of two epoxides on the ring.     

A Thermo‐ and Photo‐Switchable Ruthenium Initiator For Olefin Metathesis

A ruthenium carbene complex bearing azobenzene functionality is reported. The complex exists in the form of two isomers differing by the size of the chelate ring. Both isomers were isolated by applying kinetic or thermodynamic control during the synthesis and characterized by X‐ray diffraction analysis. The isomerization of the complex was studied by UV/Vis spectroscopy. The stable isomer was tested as a catalyst in olefin metathesis. The complex was activated at about 100 °C to promote ring‐closing and ring‐opening polymerization metathesis reactions. The activation took place also at room temperature under middle ultraviolet radiation.     

A New Synthesis of Benzofurans from Phenols via Claisen Rearrangement and Ring‐Closing Metathesis

Based on Claisen rearrangement, the double bond isomerization of O‐allyl function together with the formation of O‐vinyl function in one pot, and ring‐closing metathesis (RCM), various phenols were transformed into various benzofurans in good yields.     

Tandem catalytic carbene addition/bicyclization of enynes. One-step synthesis of fluorinated bicyclic amino esters by ruthenium catalysis

The reaction of diazo compounds with enynes, containing a fluorinated amino acid moiety, in the presence of the precatalyst Cp(Cl)Ru(COD) leads to fluorinated alkenyl bicyclo[3.1.0]hexane and [4.1.0]heptane amino acid derivatives. It is remarkable that the catalyst, in situ generated from ruthenium complex and diazo compound, completely inhibits the ring closing metathesis of enyne to the profit of tandem alkenylation/cyclopropanation with high stereoselectivity. The study shows that the Cp(Cl)Ru moiety in ruthenacyclobutane favors reductive elimination versus expected alkene metathesis. [reaction: see text]     

Studies on synthesis of quinonylidene Hoveyda‐type complexes

In a quest of redox‐switchable metathesis catalysts we attempted synthesis of ruthenium quinonylidene complexes using two synthetic pathways. First, Hoveyda‐type complexes bearing chelating benzylidene and naphthylidene ligands substituted with two alkoxy/hydroxy groups were synthesized and characterized. The catalysts were tested in model ring‐closing metathesis reactions, and displayed interesting correlations between structure and catalytic activity. Unfortunately, numerous attempts at oxidation of the complexes to derivatives of benzo‐ and naphthoquinone were unsuccessful. However, the second approach, using exchange reaction of ruthenium precursor with vinylquinone ligand, gave a transient unstable product observed with ¹H NMR. The experimental data suggest that conjugation of electron‐deficient quinones to the ruthenium centre results in intrinsically unstable species, which undergo secondary reactions under ambient conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

A Dicationic Ruthenium Alkylidene Complex for Continuous Biphasic Metathesis Using Monolith‐Supported Ionic Liquids

A dicationic ruthenium–alkylidene complex [Ru(dmf)₃(IMesH₂)(?CH‐2‐(2‐PrO)‐C₆H₄)][(BF₄)₂] ( 1 ; IMesH₂=1,3‐dimesitylimidazolin‐2‐ylidene) has been prepared and used in continuous metathesis reactions by exploiting supported ionic‐liquid phase (SILP) technology. For these purposes, ring‐opening metathesis polymerization (ROMP)‐derived monoliths were prepared from norborn‐2‐ene, tris(norborn‐5‐ene‐2‐ylmethyloxy)methylsilane, and [RuCl₂(PCy₃)₂(CHPh)] (Cy=cyclohexyl) in the presence of 2‐propanol and toluene and surface grafted with norborn‐5‐en‐2‐ylmethyl‐N,N,N‐trimethylammonium tetrafluoroborate ([NBE‐CH₂‐NMe₃][BF₄]). Subsequent immobilization of the ionic liquid (IL), 1‐butyl‐2,3‐dimethylimidazolium tetrafluoroborate ([BDMIM][BF₄]), containing ionic catalyst 1 created the SILP catalyst. The use of a second liquid transport phase, which contained the substrate and was immiscible with the IL, allowed continuous metathesis reactions to be realized. High turnover numbers (TONs) of up to 3700 obtained in organic solvents for the ring‐closing metathesis (RCM) of, for example, N,N‐diallyltrifluoroacetamide, diethyl diallylmalonate, diethyl di(methallyl)malonate, tert‐butyl‐N,N‐diallylcarbamate, N,N‐diallylacetamide, diphenyldiallylsilane, and 1,7‐octadiene, as well as in the self‐metathesis of methyl oleate, could be further increased by using biphasic conditions with [BDMIM][BF₄]/heptane. Under continuous SILP conditions, TONs up to 900 were observed. Due to the ionic character of the initiator, catalyst leaching into the transport phase was very low (<0.1 %). Finally, the IL can, together with decomposed catalyst, be removed from the monolithic support by flushing with methanol. Upon reloading with [BDMIM][BF₄]/ 1 , the recycled support material again qualified for utilization in continuous metathesis reactions.     

Application of an Enyne Metathesis/Diels–Alder Cycloaddition Sequence: A New Versatile Approach to the Syntheses of C‐Aryl Glycosides and Spiro‐C‐Aryl Glycosides

An efficient approach for the synthesis of a variety of C‐aryl and spiro‐C‐aryl glycosides is described. This diversity‐oriented strategy employed here relies on a sequential enyne metathesis to generate the 1,3‐diene moiety and Diels–Alder reaction with different dienophiles followed by aromatisation. Whereas cross‐enyne metathesis with ethylene gas is used to install the 1,3‐diene moiety at the anomeric centre for the synthesis of C‐aryl glycosides, an intramolecular enyne metathesis on the sugar enyne is performed to generate the 1,3‐diene moiety for the synthesis of spiro‐C‐aryl glycosides. Efforts to extend this strategy to the synthesis of the core structure of natural C‐aryl glycoside gilvocarcin are also described. A combination of both C‐aryl and spiro‐C‐aryl glycosides in the same moiety to combine the features thereof has also been accomplished. A tandem enyne metathesis/Diels–Alder reaction/aromatisation has also been attempted to directly access the C‐aryl glycosides in one pot albeit in low yield.     

FeCl3‐Catalyzed Ring‐Closing Carbonyl–Olefin Metathesis

Exploiting catalytic carbonyl–olefin metathesis is an ongoing challenge in organic synthesis. Reported herein is an FeCl₃‐catalyzed ring‐closing carbonyl–olefin metathesis. The protocol allows access to a range of carbo‐/heterocyclic alkenes with good efficiency and excellent trans diastereoselectivity. The methodology presents one of the rare examples of catalytic ring‐closing carbonyl–olefin metathesis. This process is proposed to take place by FeCl₃‐catalyzed oxetane formation followed by retro‐ring‐opening to deliver metathesis products.     

Novel Photoresponsive Linear,Graft, and Comb‐Like Copolymers with Azobenzene Chromophores in the Main‐Chain and/or Side‐Chain: Facile One‐Pot Synthesis and Photoresponse Properties

Novel photoresponsive linear, graft, and comb‐like copolymers with azobenzene chromophores in the main‐chain and/or side‐chain are prepared via a sequential ring‐opening metathesis polymerization (ROMP) and head‐to‐tail acyclic diene metathesis (ADMET) polymerization in a one‐pot procedure using Grubbs ruthenium‐based catalysts. The diluted solutions of these as‐prepared copolymers containing azobenzene chromophores exhibit photochemical trans–cis isomerization under the irradiation of UV light, followed by their cis–trans back‐isomerization in visible light. The rates of photoisomerization are found to be slower than those of back‐isomerization, and the rate for the comb‐like copolymer is found to be from 3 to 7 times slower than that obtained for the linear or graft copolymer. This is ascribed to the differences in structure of the copolymers and the specific location of azobenzene chromophores in the copolymer, which favor a side‐chain graft structure.

     

1,7‐Octadiene‐Assisted Tandem Multicomponent Cross‐Enyne Metathesis (CEYM)‐Diels–Alder Reactions: A Useful Alternative to Mori’s Conditions

The use of 1,7‐octadiene as an in situ source of ethylene led us to develop a novel multicomponent tandem cross‐enyne metathesis (CEYM)‐Diels–Alder reaction. The process can be considered a relay metathesis, in which the ethylene liberated in the ring‐closing metathesis (RCM) of 1,7‐octadiene initiates the tandem sequence. Aliphatic, aromatic, and fluorinated alkynes and several dienophiles are compatible with the process, which is particularly efficient with aromatic alkynes. This methodology constitutes a useful variant of Mori’s conditions in CEYM‐related reactions.     

A New Route to N‐Aryl 2‐Alkenamides,N‐Allyl N‐Aryl 2‐Alkenamides,and N‐Aryl α,β‐Unsaturated γ‐Lactams from N‐Aryl 3‐(Phenylsulfonyl)propanamides

A series of N‐aryl 2‐alkenamides were produced efficiently by treating N‐aryl 3‐(phenylsulfonyl)‐propanamides with potassium tert‐butoxide in THF at 0°C. With out isolation, it was further treated with an additional equivalent of potassium tert‐butoxide and allyl bromide to give N‐allyl N‐aryl 2‐alkenamides in one pot in good yields. Followed by a ring‐closing metathesis reaction, these N‐allyl N‐aryl 2‐alkenamides were respectively converted into corresponding N‐aryl α,β‐unsaturated γ‐lactams in moderate yields.     

Dynamic Kinetic Resolution of Homoallylic Alcohols: Application to the Synthesis of Enantiomerically Pure 5,6‐Dihydropyran‐2‐ones and δ‐Lactones

Dynamic kinetic resolution of various homoallylic alcohols with the use of Candida antarctica lipase B and ruthenium catalyst 2 afforded homoallylic acetates in high yields and with high enantioselectivity. These enantiopure acetates were further transformed into homoallylic acrylates after hydrolysis of the ester function and subsequent DMAP‐catalyzed esterification with acryloyl chloride. After ring‐closing metathesis 5,6‐dihydropyran‐2‐ones were obtained in good yields. Selective hydrogenation of the carbon? carbon double bond afforded the corresponding δ‐lactones without loss of chiral information.     

Catalyst‐Controlled Stereoselective Olefin Metathesis as a Principal Strategy in Multistep Synthesis Design: A Concise Route to (+)‐Neopeltolide

Molybdenum‐, tungsten‐, and ruthenium‐based complexes that control the stereochemical outcome of olefin metathesis reactions have been recently introduced. However, the complementary nature of these systems through their combined use in multistep complex molecule synthesis has not been illustrated. A concise diastereo‐ and enantioselective route that furnishes the anti‐proliferative natural product neopeltolide is now disclosed. Catalytic transformations are employed to address every stereochemical issue. Among the featured processes are an enantioselective ring‐opening/cross‐metathesis promoted by a Mo monoaryloxide pyrrolide (MAP) complex and a macrocyclic ring‐closing metathesis that affords a trisubstituted alkene and is catalyzed by a Mo bis(aryloxide) species. Furthermore, Z‐selective cross‐metathesis reactions, facilitated by Mo and Ru complexes, have been employed in the stereoselective synthesis of the acyclic dienyl moiety of the target molecule.     

ESIMS Studies and Calculations on Alkali‐Metal Adduct Ions of Ruthenium Olefin Metathesis Catalysts and Their Catalytic Activity in Metathesis Reactions

Electrospray ionization mass spectrometry (ESIMS) and subsequent tandem mass spectrometry (MS/MS) analyses were used to study some important metathesis reactions with the first‐generation ruthenium catalyst 1 , focusing on the ruthenium complex intermediates in the catalytic cycle. In situ cationization with alkali cations (Li⁺, Na⁺, K⁺, and Cs⁺) using a microreactor coupled directly to the ESI ion source allowed mass spectrometric detection and characterization of the ruthenium species present in solution and particularly the catalytically active monophosphine–ruthenium intermediates present in equilibrium with the respective bisphosphine–ruthenium species in solution. Moreover, the intrinsic catalytic activity of the cationized monophosphine–ruthenium complex 1 a ?K⁺ was directly demonstrated by gas‐phase reactions with 1‐butene or ethene to give the propylidene Ru species 3 a ?K⁺ and the methylidene Ru species 4 a ?K⁺, respectively. Ring‐closing metathesis (RCM) reactions of 1,6‐heptadiene ( 5 ), 1,7‐octadiene ( 6 ) and 1,8‐nonadiene ( 7 ) were studied in the presence of KCl and the ruthenium alkylidene intermediates 8 , 9 , and 10 , respectively, were detected as cationized monophosphine and bisphosphine ruthenium complexes. Acyclic diene metathesis (ADMET) polymerization of 1,9‐decadiene ( 14 ) and ring‐opening metathesis polymerization (ROMP) of cyclooctene ( 18 ) were studied analogously, and the expected ruthenium alkylidene intermediates were directly intercepted from reaction solution and characterized unambiguously by their isotopic patterns and ESIMS/MS. ADMET polymerization was not observed for 1,5‐hexadiene ( 22 ), but the formation of the intramolecularly stabilized monophosphine ruthenium complex 23 a was seen. The ratio of the signal intensities of the respective with potassium cationized monophosphine and bisphosphine alkylidene Ru species varied from [I _4a ]/[I ₄ ]=0.02 to [I _23a ]/[I ₂₃ ]=10.2 and proved to be a sensitive and quantitative probe for intramolecular π‐complex formation of the monophosphine–ruthenium species and of double bonds in the alkylidene chain. MS/MS spectra revealed the intrinsic metathesis catalytic activity of the potassium adduct ions of the ruthenium alkylidene intermediates 8 a , 9 a , 10 a , 15 a , and 19 a , but not 23 a by elimination of the respective cycloalkene in the second step of RCM. Computations were performed to provide information about the structures of the alkali metal adduct ions of catalyst 1 and the influence of the alkali metal ions on the energy profile in the catalytic cycle of the metathesis reaction.     

Synthesis of Non‐Racemic 1‐Hydroxycycloalkene‐1‐carboxylic‐Acid Derivatives by Metathesis of α,α‐Dialkylated Glycolate Derivatives

A particularly flexible general way to synthesize 1‐hydroxycycloalkene‐1‐carboxylic‐acid derivatives from 2‐(tert‐butyl)‐2‐methyl‐1,3‐dioxolan‐4‐one ( 1 ), a chiral equivalent of glycolic acid, is reported. The method is based on a double enolate alkylation of the glycolate derivative, followed by ring closing metathesis. A formal synthesis of (−)‐quinic acid is reported to demonstrate the potential of this approach.     

Cyclic poly(ε‐caprolactone) synthesized by combination of ring‐opening polymerization with ring‐closing metathesis,ring closing enyne metathesis,or “click” reaction

This article described the synthesis of cyclic poly(ε‐caprolactone) (PCL) via ring‐closing metathesis (RCM), ring closing enyne metathesis (RCEM), and “click” reaction of different difunctional linear PCL. Linear PCL precursors were prepared by ring‐opening polymerization (ROP) of ε‐caprolactone in bulk using 10‐undecen‐1‐ol or propargyl alcohol as the initiator, followed by reacting with corresponding acyl chloride containing vinyl or azido end group. The subsequent end‐to‐end intramolecular coupling reactions were performed under high dilution conditions. The successful transformation of linear PCL precursor to cyclic PCL was confirmed by Gel permeation chromatography, ¹H NMR, and Fourier transform infrared measurements. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3022–3033, 2009     

Ring‐Closing Olefin Metathesis for the Synthesis of Benzene Derivatives

Benzene derivatives were synthesized in excellent yield from 1,4,7‐trien‐3‐ols by tandem ruthenium‐catalyzed ring‐closing olefin metathesis (RCM)/dehydration. The method was extended to the tandem RCM/oxidation process to obtain phenol and aniline derivatives. This method displays many advantages over aromatic‐substitution‐based classical routes.